Exploring the relationship between emotion regulation, inhibitory control, and eating psychopathology in a non-clinical sample.

OBJECTIVE: The present study aimed to explore the relationship between difficulties in emotion regulation and deficits in inhibitory control, and the role of these processes in eating psychopathology in a non-clinical sample. We also explored the specificity in which deficits in inhibitory control may underlie eating psychopathology, namely whether they can be conceptualised as context specific or more extensive in nature. METHOD: Participants were 107 healthy individuals recruited at a major Portuguese university, aged between 18 and 43 years-old (M = 21.23, SD = 4.79). Two computerised neuropsychological tasks (i.e., emotional go/no-go and food go/no-go tasks) were used to assess response inhibition in the presence of general versus context-specific stimuli. A set of self-report measures was used to assess variables of interest such as emotion regulation and eating psychopathology. RESULTS: Results indicated higher response inhibition deficits among participants with higher difficulties in emotion regulation comparing to those with lower difficulties in emotion regulation, particularly in the context of food-related stimuli. In addition, the relationship between difficulties in emotion regulation and eating psychopathology was moderated by inhibitory control deficits in both the context of food and pleasant stimuli. CONCLUSIONS: The present findings highlight inhibitory control as an important process underlying the relationship between difficulties in emotion regulation and eating psychopathology in non-clinical samples. Findings have important implications for clinical practice and the prevention of eating psychopathology in healthy individuals and individuals with eating disorders.

The mediating role of self-criticism, experiential avoidance and negative urgency on the relationship between ED-related symptoms and difficulties in emotion regulation.

OBJECTIVE: Difficulties in emotion regulation are thought to play a transdiagnostic role across eating disorders (ED). In the current study, we explored with a path analysis the mediating role of self-criticism, experiential avoidance and negative urgency on the relationship between ED-related symptoms and dimensions of difficulties in emotion regulation. METHOD: Participants were 103 female outpatients recruited at a Portuguese ED hospital unit, diagnosed with an ED, aged 14-60 years old (M = 28.0, SD = 10.5), body mass index (BMI) ranging from 11.72 to 39.44 (M = 20.1, SD = 5.4). RESULTS: The path analysis resulted in a model with an adequate fit to the data (SRMR = 0.05; RMSEA = 0.07 [0.00, 0.12], PCLOSE = 0.269; TLI = 0.97; IFI = 0.99; GFI = 0.95). A final model in which the relationship between ED-related symptoms and dimensions of difficulties in emotion regulation was mediated by self-criticism, experiential avoidance and negative urgency, accounted for a variance of 71% for strategies, 57% for non-acceptance, 62% for impulses, 56% for goals and 20% for clarity. CONCLUSION: Results suggest that self-criticism, experiential avoidance and negative urgency, combined, are relevant in the relationship between ED-related symptoms and difficulties in emotion regulation. ED treatment and emotion regulation skills may be enhanced through the inclusion of specific components that target self-criticism, experiential avoidance and negative urgency, as they become prominent during the therapeutic process.

Astrocyte regional diversity in ALS includes distinct aberrant phenotypes with common and causal pathological processes.

Astrocytes are major contributors of motor neuron (MN) degeneration in amyotrophic lateral sclerosis (ALS). We investigated whether regional and cell maturation differences influence ALS astrocyte malfunction. Spinal and cortical astrocytes from SOD1G93A (mSOD1) 7-day-old mice were cultured for 5 and 13 days in vitro (DIV). Astrocyte aberrancies predominated in 13DIV cells with region specificity. 13DIV cortical mSOD1 astrocytes showed early morphological changes and a predominant reactive and inflammatory phenotype, while repressed proteins and genes were found in spinal cells. Inflammatory-associated miRNAs, e.g. miR-155/miR-21/miR-146a, were downregulated in the first and upregulated in the later ones. Interestingly, depleted miR-155/miR-21/miR-146a in small extracellular vesicles (sEVs/exosomes) was a common pathological feature. Cortical mSOD1 astrocytes induced late apoptosis and kinesin-1 downregulation in mSOD1 NSC-34 MNs, whereas spinal cells upregulated dynein, while decreased nNOS and synaptic-related genes. Both regional-distinct mSOD1 astrocytes enhanced iNOS gene expression in mSOD1 MNs. We provide information on the potential contribution of astrocytes to ALS bulbar-vs. spinal-onset pathology, local influence on neuronal dysfunction and their shared miRNA-depleted exosome trafficking. These causal and common features may have potential therapeutic implications in ALS. Future studies should clarify if astrocyte-derived sEVs are active players in ALS-related neuroinflammation and glial activation.

Overexpression of miR-124 in Motor Neurons Plays a Key Role in ALS Pathological Processes.

miRNA(miR)-124 is an important regulator of neurogenesis, but its upregulation in SOD1G93A motor neurons (mSOD1 MNs) was shown to associate with neurodegeneration and microglia activation. We used pre-miR-124 in wild-type (WT) MNs and anti-miR-124 in mSOD1 MNs to characterize the miR-124 pathological role. miR-124 overexpression in WT MNs produced a miRNA profile like that of mSOD1 MNs (high miR-125b; low miR-146a and miR-21), and similarly led to early apoptosis. Alterations in mSOD1 MNs were abrogated with anti-miR-124 and changes in their miRNAs mostly recapitulated by their secretome. Normalization of miR-124 levels in mSOD1 MNs prevented the dysregulation of neurite network, mitochondria dynamics, axonal transport, and synaptic signaling. Same alterations were observed in WT MNs after pre-miR-124 transfection. Secretome from mSOD1 MNs triggered spinal microglia activation, which was unno-ticed with that from anti-miR-124-modulated cells. Secretome from such modulated MNs, when added to SC organotypic cultures from mSOD1 mice in the early symptomatic stage, also coun-teracted the pathology associated to GFAP decrease, PSD-95 and CX3CL1-CX3CR1 signaling im-pairment, neuro-immune homeostatic imbalance, and enhanced miR-124 expression levels. Data suggest that miR-124 is implicated in MN degeneration and paracrine-mediated pathogenicity. We propose miR-124 as a new therapeutic target and a promising ALS biomarker in patient sub-populations.

Problematic eating behaviors and psychopathology in patients undergoing bariatric surgery: The mediating role of loss of control eating.

OBJECTIVE: This study compares different problematic eating behaviors (PEBs; objective [OBE]/subjective [SBE] binge-eating and compulsive [CG]/noncompulsive [NCG] grazing) in relation to the severity of loss of control (LOC) and psychopathology. We also investigate LOC as a mediator between PEBs and psychopathology. METHOD: This cross-sectional study assessed a group of patients before bariatric surgery (n = 163), and a group of bariatric patients 12 months or more after surgery (n = 131). Face-to-face assessment: Eating Disorders Examination for binge-eating episodes; Rep(eat) for grazing. LOC was measured by five questions answered in a 5-point Likert scale. Self-report measures: disordered eating, grazing, negative urgency, depression, anxiety, and stress. RESULTS: OBEs were reported by 26(8.8%), SBE by 29(9.8%), CG by 35(11.9%), and NCG by 36(12.2%) of patients. The different PEBs differed significantly in the severity of LOC (F(3,120)= 25.81, p < .001). Patients reporting OBEs scored higher and patients with NCG scored lower in most measures than patients with other PEBs. Patients with any PEBs scored higher in all self-report measures than those not reporting any PEBs, with statistical significance reached for uncontrolled eating (F(4,288)= 20.21, p < .001), emotional eating (F(4,288)= 23.10, p < .001), repetitive eating F(4,288)= 18.34, p < .001), and compulsive grazing (F(4,288)= 27.14, p < .001). LOC was found to be a full mediator between PEBs and psychopathology. DISCUSSION: There is no evidence that the different PEBs differ in the psychopathology severity, independently of the experience of LOC eating during the eating episodes. We show evidence for the conceptualization of different PEB, including grazing, on a continuous scale of LOC and psychopathology.

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization.

Identification of mediators triggering microglia activation and transference of noncoding microRNA (miRNA) into exosomes are critical to dissect the mechanisms underlying neurodegeneration. We used lipopolysaccharide- (LPS-) induced N9 microglia activation to explore new biomarkers/signaling pathways and to identify inflammatory miRNA (inflamma-miR) in cells and their derived exosomes. Upregulation of iNOS and MHC-II (M1-markers) and downregulation of arginase 1, FIZZ1 (M2-markers), and CX3CR1 (M0/M2 polarization) confirmed the switch of N9 LPS-treated cells into the M1 phenotype, as described for macrophages/microglia. Cells showed increased proliferation, activated TLR4/TLR2/NF-κB pathway, and enhanced phagocytosis, further corroborated by upregulated MFG-E8. We found NLRP3-inflammasome activation in these cells, probably accounting for the increased extracellular content of the cytokine HMGB1 and of the MMP-9 we have observed. We demonstrate for the first time that the inflamma-miR profiling (upregulated miR-155 and miR-146a plus downregulated miR-124) in M1 polarized N9 cells, noticed by others in activated macrophages/microglia, was replicated in their derived exosomes, likely regulating the inflammatory response of recipient cells and dissemination processes. Data show that LPS-treated N9 cells behave like M1 polarized microglia/macrophages, while providing new targets for drug discovery. In particular, the study yields novel insights into the exosomal circulating miRNA during neuroinflammation important for emerging therapeutic approaches targeting microglia activation.

The prevalence of binge eating disorder in a sample of college students in the north of Portugal.

Binge eating disorder (BED) has important associated comorbidities and has been recently considered as a diagnostic category in the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition. This study investigates the prevalence of BED in a sample of college students using a two-stage design. Between October 2008 and July 2009, 805 students attending a public college campus completed the Questionnaire on Eating and Weight Patterns - Revised to screen for possible cases. Eighty-five students meeting key criteria for BED were invited for a second stage interview using the Eating Disorder Examination. At stage 1, 9.6% of the subjects reported binge eating episodes. At stage 2, a prevalence rate of 0.5% for BED was found, and 1% if the criterion for large amount of food was excluded.

Loss of control eating and weight outcomes after bariatric surgery: a study with a Portuguese sample.

The present study aim is to investigate the frequency of loss of control eating (LOC) episodes in three groups with different assessment times: one before, one at short and one at long-term after bariatric surgery; as well as to explore the association of postoperative problematic eating behaviors and weight outcomes and psychological characteristics. This cross-sectional study compared a group of preoperative bariatric surgery patients (n = 176) and two postoperative groups, one at short-term with <2 years follow-up (n = 110), and one at long-term >2 years follow-up (n = 53). Assessments included the EDE diagnostic interview and a set of self-report measures assessing eating disordered symptomatology, depression, and body image. We found the presence of LOC in 26.7 and 16.9 % of the pre-operative and long-term patients, respectively, and in about 11.8% of the short-term patients. One patient (0.9%) reported objective binge eating episodes at short-time, but subjective binge eating episodes were present in about 10% of the patients in all groups. LOC eating was related with the highest BMIs, the least weight loss, most weight regain, and most psychological impairment in the long-term assessments, but not at short-term. Despite the lower frequencies of disordered eating behavior in the short-term group, patients reporting LOC seem to represent a subgroup of individuals with poorest outcomes after surgery and most psychological distress.

Tricellulin expression in brain endothelial and neural cells.

Tricellulin is a tight junction (TJ) protein, which is not only concentrated at tricellular contacts but also present at bicellular contacts between epithelial tissues. We scrutinized the brain for tricellulin expression in endothelial and neural cells by using real-time polymerase chain reaction, Western blot and immunohistochemical and immunocytochemical analysis of cultured brain cells and paraffin sections of brain. Tricellulin mRNA was detected in primary cultures and in a cell line of human brain microvascular endothelial cells. Protein expression was confirmed by Western blot and immunofluorescence analysis, which further highlighted the localization of tricellulin in the cell membrane at tricellular and along bicellular contacts, and in the nucleus and perinuclear region. Compared with the well-studied TJ protein, zonula occludens-1, tricellulin expression was less marked at the cell membrane but more evident in the nuclear and perinuclear regions. The presence of tricellulin in cultured endothelial cells was corroborated by immunohistochemical and immunofluorescence staining in brain blood vessels, where it was colocalized with another TJ protein, claudin-5. Tricellulin mRNA was detected in neurons and astrocytes, whereas protein expression was observed in astrocytes but not in neurons, as shown by immunofluorescence analysis. This study reveals the presence and subcellular distribution of tricellulin in brain endothelial cells, both in vitro and in situ and its colocalization with other relevant TJ proteins. Moreover, it demonstrates the expression of the protein in astrocytes opening new avenues for future research to establish the biological significance of tricellulin expression in glial cells.

Cross-talk between neurons and astrocytes in response to bilirubin: early beneficial effects.

Hyperbilirubinemia remains one of the most frequent clinical diagnoses in the neonatal period. This condition may lead to the deposition of unconjugated bilirubin (UCB) in the central nervous system, causing nerve cell damage by molecular and cellular mechanisms that are still being clarified. To date, all the studies regarding bilirubin-induced neurological dysfunction were performed in monotypic nerve cell cultures. The use of co-cultures, where astrocyte-containing culture inserts are placed on the top of neuron cultures, provides the means to directly evaluate the cross-talk between these two different cell types. Therefore, this study was designed to evaluate whether protective or detrimental effects are produced by astrocytes over UCB-induced neurodegeneration. Our experimental model used an indirect co-culture system where neuron-to-astrocyte signaling was established concomitantly with the 24 h exposure to UCB. In this model astrocytes abrogated the well-known UCB-induced neurotoxic effects by preventing the loss of cell viability, dysfunction and death by apoptosis, as well as the impairment of neuritic outgrowth. To this protection it may have accounted the induced expression of the multidrug resistance-associated protein 1 and the 3.5-fold increase in the values of S100B, when communication between both cells was established independently of UCB presence. In addition, the presence of astrocytes in the neuronal environment preserved the UCB-induced increase in glutamate levels, but raised the basal concentrations of nitric oxide and TNF-α although no UCB effects were noticed. Our data suggest that bidirectional signalling during astrocyte-neuron recognition exerts pro-survival effects, stimulates neuritogenesis and sustains neuronal homeostasis, thus protecting cells from the immediate UCB injury. These findings may help explain why irreversible brain damage usually develops only after the first day of post-natal life.

Guided self-help CBT treatment for bulimic disorders: effectiveness and clinically significant change.

The aim of this study was to test the effectiveness of a cognitive-behavioral guided self-help treatment program for bulimia nervosa and similar disorders. Participants were assessed at the beginning and end of treatment, and at 6 months follow-up, using the Eating Disorder Examination Questionnaire (EDE-Q), the Outcome-Questionnaire-45 (OQ-45), and the Beck Depression Inventory (BDI). Forty-two participants from an eating disorders treatment service participated in this study. This study followed a one-group repeated measures naturalistic design with no control group. Results showed a significant reduction in EDE scores, OQ-45 and BDI. Clinically significant change occurred for the majority of participants. Cognitive-behavioral self-help treatment may be of value as an initial treatment for bulimia nervosa and similar disorders such as binge eating disorder.

Selective vulnerability of rat brain regions to unconjugated bilirubin.

Hippocampus is one of the brain regions most vulnerable to unconjugated bilirubin (UCB) encephalopathy, although cerebellum also shows selective yellow staining in kernicterus. We previously demonstrated that UCB induces oxidative stress in cortical neurons, disruption of neuronal network dynamics, either in developing cortical or hippocampal neurons, and that immature cortical neurons are more prone to UCB-induced injury. Here, we studied if immature rat neurons isolated from cortex, cerebellum and hippocampus present distinct features of oxidative stress and cell dysfunction upon UCB exposure. We also explored whether oxidative damage and its regulation contribute to neuronal dysfunction induced by hyperbilirubinemia, considering neurite extension and ramification, as well as cell death. Our results show that UCB induces nitric oxide synthase expression, as well as production of nitrites and cyclic guanosine monophosphate in immature neurons, mainly in those from hippocampus. After exposure to UCB, hippocampal neurons presented the highest content of reactive oxygen species, disruption of glutathione redox status and cell death, when compared to neurons from cortex or cerebellum. In particular, the results indicate that cells exposed to UCB undertake an adaptive response that involves DJ-1, a multifunctional neuroprotective protein implicated in the maintenance of cellular oxidation status. However, longer neuronal exposure to UCB caused down-regulation of DJ-1 expression, especially in hippocampal neurons. In addition, a greater impairment in neurite outgrowth and branching following UCB treatment was also noticed in immature neurons from hippocampus. Interestingly, pre-incubation with N-acetylcysteine, a precursor of glutathione synthesis, protected neurons from UCB-induced oxidative stress and necrotic cell death, preventing DJ-1 down-regulation and neuritic impairment. Taken together, these data point to oxidative injury and disruption of neuritic network as hallmarks in hippocampal susceptibility to UCB. Most importantly, they also suggest that local differences in glutathione content may account to the different susceptibility between brain regions exposed to UCB.

Challenges in the Development of Drug Delivery Systems Based on Small Extracellular Vesicles for Therapy of Brain Diseases.

Small extracellular vesicles (sEVs) have ∼30-200 nm diameter size and may act as carriers of different cargoes, depending on the cell of origin or on the physiological/pathological condition. As endogenous nanovesicles, sEVs are important in intercellular communication and have many of the desirable features of an ideal drug delivery system. sEVs are naturally biocompatible, with superior targeting capability, safety profile, nanometric size, and can be loaded with both lipophilic and hydrophilic agents. Because of their biochemical and physical properties, sEVs are considered a promising strategy over other delivery vehicles in the central nervous system (CNS) since they freely cross the blood-brain barrier and they can be directed to specific nerve cells, potentiating a more precise targeting of their cargo. In addition, sEVs remain stable in the peripheral circulation, making them attractive nanocarrier systems to promote neuroregeneration. This review focuses on the recent progress in methods for manufacturing, isolating, and engineering sEVs that can be used as a therapeutic strategy to overcome neurodegeneration associated with pathologies of the CNS, with particular emphasis on Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis diseases, as well as on brain tumors.

Differences in Immune-Related Genes Underlie Temporal and Regional Pathological Progression in 3xTg-AD Mice.

The prevalence of Alzheimer's disease (AD), the most common cause of age-associated dementia, is estimated to increase over the next decades. Evidence suggests neuro-immune signaling deregulation and risk genes beyond the amyloid-ß (Aß) deposition in AD pathology. We examined the temporal profile of inflammatory mediators and microglia deactivation/activation in the brain cortex and hippocampus of 3xTg-AD mice at 3- and 9-month-old. We found upregulated APP processing, decreased expression of CD11b, CX3CR1, MFG-E8, TNF-α, IL-1ß, MHC-II and C/EBP-α and increased miR-146a in both brain regions in 3-month-old 3xTG-AD mice, suggestive of a restrictive regulation. Enhanced TNF-α, IL-1ß, IL-6, iNOS, SOCS1 and Arginase 1 were only present in the hippocampus of 9-month-old animals, though elevation of HMGB1 and reduction of miR-146a and miR-124 were common features in the hippocampus and cortex regions. miR-155 increased early in the cortex and later in both regions, supporting its potential as a biomarker. Candidate downregulated target genes by cortical miR-155 included Foxo3, Runx2 and CEBPß at 3 months and Foxo3, Runx2 and Socs1 at 9 months, which are implicated in cell survival, but also in Aß pathology and microglia/astrocyte dysfunction. Data provide new insights across AD state trajectory, with divergent microglia phenotypes and inflammatory-associated features, and identify critical targets for drug discovery and combinatorial therapies.

Vulnerability through the Eyes of People Attended by a Portuguese Community-Based Association: A Thematic Analysis.

Vulnerability is associated with the individual's social and biological conditions, but also the conditions of their enveloping environment and society, leading to terms such as vulnerable populations or risk groups. This study aimed to give a voice to people with experiences of vulnerability and explore their perspectives, using a descriptive qualitative design. Purportedly vulnerable adults were recruited and interviewed with semi-structured questions on vulnerability. Data were organized, using WebQDA software, and submitted to thematic content analysis, as proposed by Clark and Braun, which generated a thematic tree. The study included six men and six women with a mean age of 43.8 [SD = 14.17] years old. Thematic analysis generated three themes: (1) Conceptions about vulnerability, (2) Barriers imposed by vulnerability, and (3) Strategies for dealing with vulnerability. The results highlight that vulnerability is a highly dynamic process of openness to circumstances that influence individual outcomes. However, there is a lack of conceptual clarity. Although being vulnerable is perceived as something negative, we need to transform the social mindset, because vulnerability also has the potential to change priorities in life for the better.

Intrathecal Injection of the Secretome from ALS Motor Neurons Regulated for miR-124 Expression Prevents Disease Outcomes in SOD1-G93A Mice.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with short life expectancy and no effective therapy. We previously identified upregulated miR-124 in NSC-34-motor neurons (MNs) expressing human SOD1-G93A (mSOD1) and established its implication in mSOD1 MN degeneration and glial cell activation. When anti-miR-124-treated mSOD1 MN (preconditioned) secretome was incubated in spinal cord organotypic cultures from symptomatic mSOD1 mice, the dysregulated homeostatic balance was circumvented. To decipher the therapeutic potential of such preconditioned secretome, we intrathecally injected it in mSOD1 mice at the early stage of the disease (12-week-old). Preconditioned secretome prevented motor impairment and was effective in counteracting muscle atrophy, glial reactivity/dysfunction, and the neurodegeneration of the symptomatic mSOD1 mice. Deficits in corticospinal function and gait abnormalities were precluded, and the loss of gastrocnemius muscle fiber area was avoided. At the molecular level, the preconditioned secretome enhanced NeuN mRNA/protein expression levels and the PSD-95/TREM2/IL-10/arginase 1/MBP/PLP genes, thus avoiding the neuronal/glial cell dysregulation that characterizes ALS mice. It also prevented upregulated GFAP/Cx43/S100B/vimentin and inflammatory-associated miRNAs, specifically miR-146a/miR-155/miR-21, which are displayed by symptomatic animals. Collectively, our study highlights the intrathecal administration of the secretome from anti-miR-124-treated mSOD1 MNs as a therapeutic strategy for halting/delaying disease progression in an ALS mouse model.

Emerging Role of miR-21-5p in Neuron-Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with neuron-glia dysfunction and dysregulated miRNAs. We previously reported upregulated miR-124/miR-21 in AD neurons and their exosomes. However, their glial distribution, phenotypic alterations and exosomal spread are scarcely documented. Here, we show glial cell activation and miR-21 overexpression in mouse organotypic hippocampal slices transplanted with SH-SY5Y cells expressing the human APP695 Swedish mutation. The upregulation of miR-21 only in the CSF from a small series of mild cognitive impairment (MCI) AD patients, but not in non-AD MCI individuals, supports its discriminatory potential. Microglia, neurons, and astrocytes differentiated from the same induced pluripotent stem cells from PSEN1ΔE9 AD patients all showed miR-21 elevation. In AD neurons, miR-124/miR-21 overexpression was recapitulated in their exosomes. In AD microglia, the upregulation of iNOS and miR-21/miR-146a supports their activation. AD astrocytes manifested a restrained inflammatory profile, with high miR-21 but low miR-155 and depleted exosomal miRNAs. Their immunostimulation with C1q + IL-1α + TNF-α induced morphological alterations and increased S100B, inflammatory transcripts, sAPPß, cytokine release and exosomal miR-21. PPARα, a target of miR-21, was found to be repressed in all models, except in neurons, likely due to concomitant miR-125b elevation. The data from these AD models highlight miR-21 as a promising biomarker and a disease-modifying target to be further explored.

Astrocyte reactivity to unconjugated bilirubin requires TNF-α and IL-1ß receptor signaling pathways.

Jaundice and sepsis are common neonatal conditions that can lead to neurodevelopment sequelae, namely if present at the same time. We have reported that tumor necrosis factor (TNF)-α and interleukin (IL)-1ß are produced by cultured neurons and mainly by glial cells exposed to unconjugated bilirubin (UCB). The effects of these cytokines are mediated by cell surface receptors through a nuclear factor (NF)-κB-dependent pathway that we have showed to be activated by UCB. The present study was designed to evaluate the role of TNF-α and IL-1ß signaling on astrocyte reactivity to UCB in rat cortical astrocytes. Exposure of astrocytes to UCB increased the expression of both TNF-α receptor (TNFR)1 and IL-1ß receptor (IL-1R)1, but not TNFR2, as well as their activation, observed by augmented binding of receptors' molecular adaptors, TRAF2 and TRAF6, respectively. Silencing of TNFR1, using siRNA technology, or blockade of IL-1ß cascade, using its endogenous antagonist, IL-1 receptor antagonist (IL-1ra), prevented UCB-induced cytokine release and NF-κB activation. Interestingly, lack of TNF-α signal transduction reduced UCB-induced cell death for short periods of incubation, although an increase was observed after extended exposure; in contrast, inhibition of IL-1ß cascade produced a sustained blockade of astrocyte injury by UCB. Together, our data show that inflammatory pathways are activated during in vitro exposure of rat cortical astrocytes to UCB and that this activation is prolonged in time. This supports the concept that inflammatory pathways play a role in brain damage by UCB, and that they may represent important pharmacological targets.

Exploring Correlates of Loss of Control Eating in a Nonclinical Sample.

OBJECTIVE: Loss of control (LOC) eating has been directly related to the core aspects of the psychopathology of eating disorders and to different dimensions of emotion and behavior regulation and self-criticism. This study investigates a model representing the interplay between these dimensions to understand LOC eating among a nonclinical sample. METHODS: A total of 341 participants, recruited in a college campus (mean age 23.21, SD = 6.02), completed a set of self-report measures assessing LOC eating, weight suppression, psychopathology of eating disorders, depression, negative urgency, emotion regulation difficulties, and self-criticism. Path analysis modeling tested a hypothesized model with 3 paths for LOC eating as follows: (1) psychopathology of eating disorders; (2) emotion and behavior regulation; and (3) interplay between these paths. RESULTS: We found goodness-of-fit indexes to our data: χ2 = 17.11, df = 10, Comparative Fit Index (CFI) = 0.99, Tucker-Lewis index (TLI) = 0.98, Root Mean Square Error Approximation (RMSEA) = 0.045, Standardized Root Mean Square Residual (SRMR) = 0.041, suggesting that: (1) participants with higher weight suppression showed higher degrees of the psychopathology of eating disorders, which was linked to higher levels of LOC eating; (2) self-criticism was a mediator between emotion regulation and depression/negative urgency; (3) self-criticism was a mediator between emotion regulation and disorder eating, which was significantly associated with LOC eating via increased negative urgency. CONCLUSION: Our model shows that LOC eating occurs for individuals with the psychopathology of higher eating disorders who experience depressive symptoms and act rashly under distress for their inability to cope adequately with negative feelings of self-devaluation. These findings point to the importance of negative self-evaluations and feelings of inadequacy or worthlessness to understand LOC eating among college students.

Eating behaviors and weight outcomes in bariatric surgery patients amidst COVID-19.

BACKGROUND: Recent studies suggest that eating habits are an area particularly affected by the lockdown imposed by many countries to curb the COVID-19 epidemic. Individuals that received bariatric surgery may represent a particularly susceptible population to the adverse effects of lockdown for its potential impact on eating, psychological, and weight loss outcomes. OBJECTIVES: This study seeks to investigate the incremental impact of COVID-19 lockdown on treatment outcomes of postbariatric patients in the risk period for weight regain. SETTING: Main hospital center. METHODS: This work uses data from an ongoing longitudinal study of bariatric patients assessed before surgery (T0), 1.5 years after sugery (T1), and 3 years after surgery (T2). Two independent groups were compared: the COVID-19_Group (n = 35) where T0 and T1 assessments were conducted before the pandemic started and T2 assessment was conducted at the end of the mandatory COVID-19 lockdown; and the NonCOVID-19_Group (n = 66), covering patients who completed T0, T1, and T2 assessments before the epidemic began. Assessment included self-report measures for disordered eating, negative urgency, depression, anxiety, stress, and weight outcomes. RESULTS: General linear models for repeated measures showed that the COVID-19_Group presented significantly higher weight concern (F = 8.403, P = .005, ƞ2p = .094), grazing behavior (F = 7.166, P = .009, ƞ2p = .076), and negative urgency (F = 4.522, P = .036, ƞ2p = .05) than the NonCOVID-19_Group. The COVID-19_Group also showed less total weight loss (F = 4.029, P = .05, ƞ2p = .04) and larger weight regain at T2, with more COVID-19_Group participants experiencing excessive weight regain (20% versus 4.5%). CONCLUSION: These results show evidence for the impact of the coronavirus outbreak on eating-related psychopathology and weight outcomes in postbariatric surgery patients.